BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Objective To evaluate the efficacy and safety of polyethylene glycol electrolyte powder(PEG)combined with linaclotide(Lin)for bowel preparation in elderly constipated patients before colonoscopy.Methods In this prospective,randomized controlled trial,90 elderly patients with constipation undergoing colonoscopy were recruited at our hospital from June 2022 to December 2023.Participants were randomly assigned to three groups(n=30 each):PEG-3L alone,PEG-3L+Lin,and PEG-2L+Lin.Primary outcome was Boston Bowel Preparation Scale(BBPS)score and secondary outcomes included adverse event rates,colonoscopy completion rate,withdrawal time,and polyp detection rate.Statistical analysis was performed using independent t-tests and chi-square tests.Results The PEG-3L+Lin group achieved significantly higher BBPS scores than both PEG-3L alone and PEG-2L+Lin groups did(both P<0.001).The PEG-2L+Lin group also outperformed the PEG-3L alone group in cleansing efficacy(90.0%vs.76.7%,P=0.008).The PEG-2L+Lin group demonstrated the best tolerability and lowest adverse event rate,the PEG-3L group had the longest withdrawal time(P<0.05),but the three groups showed no significant difference in polyp detection rates.Conclusion PEG combined with linaclotide significantly improves bowel cleansing in elderly constipated patients.PEG-2L+Lin regimen provides optimal balance between efficacy,safety,and tolerability,making it a preferable choice for this population.

Objective To evaluate the efficacy and safety of polyethylene glycol electrolyte powder(PEG)combined with linaclotide(Lin)for bowel preparation in elderly constipated patients before colonoscopy.Methods In this prospective,randomized controlled trial,90 elderly patients with constipation undergoing colonoscopy were recruited at our hospital from June 2022 to December 2023.Participants were randomly assigned to three groups(n=30 each):PEG-3L alone,PEG-3L+Lin,and PEG-2L+Lin.Primary outcome was Boston Bowel Preparation Scale(BBPS)score and secondary outcomes included adverse event rates,colonoscopy completion rate,withdrawal time,and polyp detection rate.Statistical analysis was performed using independent t-tests and chi-square tests.Results The PEG-3L+Lin group achieved significantly higher BBPS scores than both PEG-3L alone and PEG-2L+Lin groups did(both P<0.001).The PEG-2L+Lin group also outperformed the PEG-3L alone group in cleansing efficacy(90.0%vs.76.7%,P=0.008).The PEG-2L+Lin group demonstrated the best tolerability and lowest adverse event rate,the PEG-3L group had the longest withdrawal time(P<0.05),but the three groups showed no significant difference in polyp detection rates.Conclusion PEG combined with linaclotide significantly improves bowel cleansing in elderly constipated patients.PEG-2L+Lin regimen provides optimal balance between efficacy,safety,and tolerability,making it a preferable choice for this population.

Objective Analyzes the grouping effect and its influencing factors under DRG payment,provides reference for the reform of DRG payment.Methods Evaluates the effectiveness of DRG grouping using Coefficient of Variation(CV)and Reduction in Variance;using Value of Structure of Variation and Degree of Structure Variation,analyzes hospitalization costs structure changes of different DRG groups,and calculates the degree of correlation between average hospitalization costs through grey relational analysis;using non parametric tests and multiple regression to analyze the influencing factors of hospitalization cost.Results DRG grouping effect was not good,inter-group heterogeneity was not obvious;the structure of hospitalization expenses is unreasonable,and the proportion of consumables expenses is too high,ranking first in the grey correlation degree of hospitalization expenses,comprehensive medical service fees and treatment fees rank third and fifth respectively;the main factors affecting hospitalization costs are treatment methods,length of stay,presence of complications,and first hospitalization,the difference is statistically significant(P＜0.05).Conclusion More grouping nodes or higher CV value standards should be added to enhance the grouping effect of gastric cancer DRG;optimize the structure of hospitalization costs to reflect the labor and technical value of medical personnel;strengthen internal management and control the unreasonable use of drugs and consumables.

Objective:This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism.Method:Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted.Results:The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) μU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) μU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps ( OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions:There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.

BACKGROUND:Most of the silver coating materials prepared using active screen plasma technology in the past do not involve the nanotechnology field.The formed silver coating is in a"thin film"form,which is coated on the surface of the substrate,and the distribution of silver particles on the surface is uneven.Its long-term antibacterial ability is challenged. OBJECTIVE:To prepare nano silver coatings capable of being"buried"within stainless steel(SS)substrates using active screen plasma surface modification(ASPSM)and to observe antibacterial activity. METHODS:The nano-silver coating was prepared by ASPSM technique on stainless steel substrate.Three groups of coating samples were prepared by adjusting the bombardment time(1,2,and 4 hours),which were denoted as 1 h-Ag-ASPSM@SS,2 h-Ag-ASPSM@SS and 4 h-Ag-ASPSM@SS,respectively.The antibacterial activity of the coatings was analyzed by antibacterial ring test and Gram staining.The antibiotic coating samples of gentamicin combined with vancomycin were prepared by using stainless steel as substrate and were recorded as ACNs.Stainless steel,2 h-Ag-ASPSM@SS,and ACNs were inserted into Staphylococcus aureus or Pseudomonas aeruginosa suspension,respectively.The long-acting(84 days)antibacterial activity of the samples was analyzed by coating plate method.Bone marrow mesenchymal stem cells were co-cultured with stainless steel,2 h-Ag-ASPSM@SS,and ACNs,respectively.CCK-8 assay,dead/alive staining,and lactate dehydrogenase activity of cell supernatant were detected.Stainless steel,2 h-Ag-ASPSM@SS,and ACNs were taken after continuous exposure to Staphylococcus aureus suspension for 12 weeks.The amount of residual viable bacteria on the surface of the material was evaluated by spread plate method.Vancomycin drug sensitive disk method was used to evaluate the resistance of residual live bacteria on the surface of materials. RESULTS AND CONCLUSION:(1)With increasing bombardment time,the diameter of nano silver on the sample surface and the silver content in the coating gradually increased.Among them,the 2 h-Ag-ASPSM@SS exhibited the highest surface silver content while forming uniformly spherical nanoparticles.(2)Antibacterial ring test and Gram staining results demonstrated that compared with 1 h-Ag-ASPSM@SS and 4 h-Ag-ASPSM@SS,the 2 h-Ag-ASPSM@SS exhibited better inhibitory effect on Staphylococcus aureus and pseudomonas aeruginosa.After co-culturing with bacteria for 42 and 84 days,the number of viable bacteria on the spread plate method was significantly lower in the 2 h-Ag-ASPSM@SS group compared to the stainless steel and ACNs groups.After co-culturing with Staphylococcus aureus for 84 days and Pseudomonas aeruginosa for 42 days,the number of viable bacteria on the surface of the eluate from the ACNs group was higher than that of the stainless steel group.(3)CCK-8 assay,live/dead staining and lactate dehydrogenase activity of cell supernatant displayed that 2 h-Ag-ASPSM@SS did not have obvious cytotoxicity.ACNs showed obvious cytotoxicity.(4)After co-culture with Staphylococcus aureus for 12 weeks,the residual viable bacteria on the surface of 2 h-Ag-ASPSM@SS group was less than that of stainless steel group,and the residual viable bacteria on the surface of the ACNs group was more than that of stainless steel group.Compared with the stainless steel group,the sensitivity to vancomycin was significantly decreased in the ACNs group(P＜0.001),and there was no significant change in sensitivity to vancomycin in 2 h-Ag-ASPSM@SS group(P＞0.05).(5)The above results indicate that the silver nanoparticle coated stainless steel greatly improves the deposition efficiency of silver nanoparticles on the stainless steel surface and has long-lasting antibacterial properties and good cell compatibility.

Objective:This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism.Method:Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted.Results:The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) μU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) μU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps ( OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions:There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.

Objective:To investigate the expression level of transcription factor dimerization partner 2 (TFDP2) in the placentas of women with preeclampsia, and analyze its effect on the apoptosis of trophoblast cells.Methods:Placental tissues from thirty puerperae with preeclampsia who gave birth by cesarean section in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between January 2018 and December 2022 (preeclampsia group) and 30 healthy puerperae undergoing cesarean section during the same period (control group) were retrospectively selected. Immunohistochemistry was used to localize TFDP2 in the placental tissues. Real-time quantitative-polymerase chain reaction (qRT-PCR) and Western blot were used to detect the differences in expression of TFDP2 at mRNA and protein levels in placental tissues between the two groups. Forskolin-exposed BeWo cells were transfected with small interfering RNA (siRNA) to knockdown TFDP2 and the changes in the expression of apoptosis-related indicators, B cell lymphoma 2 (Bcl2) and Bcl2 associated X (Bax), at protein and mRNA levels were analyzed by Western blot and qRT-PCR, respectively. Besides, the change in the apoptosis level of BeWo cells was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry. Downstream signaling pathways were analyzed to understand the involved molecular mechanisms. Two independent samples t-test, Wilcoxon rank-sum test, and Chi-square test were used for statistical analysis. Results:TFDP2 was mostly localized in the syncytiotrophoblasts and the extravillous trophoblasts in the normal placentas. TFDP2 expression in the syncytiotrophoblasts was lower in the preeclampsia group than in the control group at both mRNA (0.722±0.239 vs. 1.000±0.348, t=3.61, P=0.001) and protein (0.728±0.185 vs. 1.000±0.206, t=2.41, P=0.037) levels. Comparing the group without knockdown of TFDP2, the knockdown of TFDP2 in BeWo cells elevated the Bax/Bcl2 ratio (mRNA: 1.755±0.452 vs. 1.000±0.279, t=3.48, P=0.006; protein: 3.206±0.922 vs. 1.000±0.290, t=3.95, P=0.017), and increased cell apoptosis both in number and ratio (TUNEL staining: 4.556±1.740 vs. 2.444±1.130, t=3.05, P=0.008; flow cytometry: 21.37%±1.66% vs. 12.61%±0.38%, t=8.92, P=0.001). Furthermore, following TFDP2 knockdown, a decrease in the phosphorylation activity of catalytic subunit of protein kinase A (PKAc) at the Thr197 site was observed in the cytoplasm of BeWo cells (0.466±0.035 vs. 1.000±0.075, t=11.19, P<0.001) and a reduction in the expression of β-catenin in the cell nucleus was also detected (0.250±0.093 vs. 1.000±0.269, t=4.57, P=0.010). Conclusion:The expression of TFDP2 decreased significantly in the placentas of patients with preeclampsia, which may promote the apoptosis of syncytiotrophoblasts by inhibiting the PKAc/β-catenin signaling pathway.

Objective Analyzes the grouping effect and its influencing factors under DRG payment,provides reference for the reform of DRG payment.Methods Evaluates the effectiveness of DRG grouping using Coefficient of Variation(CV)and Reduction in Variance;using Value of Structure of Variation and Degree of Structure Variation,analyzes hospitalization costs structure changes of different DRG groups,and calculates the degree of correlation between average hospitalization costs through grey relational analysis;using non parametric tests and multiple regression to analyze the influencing factors of hospitalization cost.Results DRG grouping effect was not good,inter-group heterogeneity was not obvious;the structure of hospitalization expenses is unreasonable,and the proportion of consumables expenses is too high,ranking first in the grey correlation degree of hospitalization expenses,comprehensive medical service fees and treatment fees rank third and fifth respectively;the main factors affecting hospitalization costs are treatment methods,length of stay,presence of complications,and first hospitalization,the difference is statistically significant(P＜0.05).Conclusion More grouping nodes or higher CV value standards should be added to enhance the grouping effect of gastric cancer DRG;optimize the structure of hospitalization costs to reflect the labor and technical value of medical personnel;strengthen internal management and control the unreasonable use of drugs and consumables.

Objective Analyzes the grouping effect and its influencing factors under DRG payment,provides reference for the reform of DRG payment.Methods Evaluates the effectiveness of DRG grouping using Coefficient of Variation(CV)and Reduction in Variance;using Value of Structure of Variation and Degree of Structure Variation,analyzes hospitalization costs structure changes of different DRG groups,and calculates the degree of correlation between average hospitalization costs through grey relational analysis;using non parametric tests and multiple regression to analyze the influencing factors of hospitalization cost.Results DRG grouping effect was not good,inter-group heterogeneity was not obvious;the structure of hospitalization expenses is unreasonable,and the proportion of consumables expenses is too high,ranking first in the grey correlation degree of hospitalization expenses,comprehensive medical service fees and treatment fees rank third and fifth respectively;the main factors affecting hospitalization costs are treatment methods,length of stay,presence of complications,and first hospitalization,the difference is statistically significant(P＜0.05).Conclusion More grouping nodes or higher CV value standards should be added to enhance the grouping effect of gastric cancer DRG;optimize the structure of hospitalization costs to reflect the labor and technical value of medical personnel;strengthen internal management and control the unreasonable use of drugs and consumables.